The right ventricle in scleroderma (2013 Grover Conference Series)

Abstract

Pulmonary arterial hypertension (PAH) results from severe remodeling of the distal lung vessels leading irremediably to death through right ventricular (RV) failure. PAH (Group 1 of the World Health Organization classification of pulmonary hypertension) can be idiopathic (IPAH) or associated with other disorders, such as connective tissue diseases. Prominent among the latter is systemic sclerosis (SSc), a heterogeneous disorder characterized by endothelium dysfunction, dysregulation of fibroblasts resulting in excessive collagen production, and immune abnormalities. For as-yet-unknown reasons, SSc-associated PAH (SSc-PAH) carries a significantly worse prognosis compared with any other form of PAH in Group 1, including IPAH. We have previously shown that patients with SSc-PAH have a median survival of only 3 years, compared with 8 years for IPAH, despite modern PAH therapy. Because death is principally due to RV failure, we speculated that RV adaptation to PAH differed between the two entities due to disparate pulmonary artery loading, perhaps from vessel stiffening, or intrinsic RV myocardial disease that might limit function and adaptation to high afterload. In SSc, RV function may also be impaired by inflammatory processes, excess fibrosis of the myocardium, or altered angiogenesis, which may all contribute to impaired contractile reserve exacerbating cardiopulmonary impedance mismatch. This is now suggested by recent findings from our group that demonstrate that, although pulmonary vascular load may be similar between patients with IPAH and those with SSc-PAH, the latter display reduced myocardial contractility as assessed by pressure-volume loop measurements. This review focuses on fundamental hemodynamic, structural, and functional differences in RV from patients with SSc-PAH compared with IPAH, which may account for survival discrepancies between the two populations. Possible underlying basic mechanisms are discussed.

Keywords: pulmonary arterial hypertension; right ventricle; right ventricle-pulmonary vascular coupling.

Figures

Figure 1

Pulmonary vascular resistance-compliance (RC) relationship (A) in the pulmonary circulation and (B) in the systemic circulation. C, Resistance-compliance product for the pulmonary and systemic vasculature plot against mean arterial pressure. D, Resistance-compliance relationship in patients with severe pulmonary fibrosis. SPH = secondary pulmonary hypertension; PH = pulmonary hypertension. Reproduced with permission from Tedford et al.

Figure 2

Pulmonary vascular resistance-compliance relationship in patients with systemic sclerosis–associated pulmonary arterial hypertension (SSc-PAH) versus patients with ideopathic pulmonary arterial hypertension (IPAH). Reproduced with permission from Tedford et al.

Figure 3

A, Right ventricle (RV) and left ventricle (LV) myocardial perfusion reserve index (MPRI) in control, non–pulmonary arterial hypertension (PAH), and PAH groups. Asterisk indicates P < 0.05 versus control group. There was no difference in RV MPRI between control subjects and patients with SSc but unconfirmed PAH (the non-PAH group). B, Relationship between mean pulmonary artery pressure (mPAP) and RV MPRI ( = −0.59; P = 0.036) in 25 patients with known or suspected PAH. A similar relationship was found with LV MPRI and between RV MPRI and RV mass and ventricle mass index (not shown). Reproduced with permission from Vogel-Claussen et al. Copyright the Radiological Society of North America.

Figure 4

A, Immunostaining of myocardial capillaries in patients with heart failure with preserved ejection fraction (HFpEF), systemic sclerosis (SSc) without pulmonary arterial hypertension (PAH), and SSc-PAH, at low (upper panels) and high (lower panels) magnification. B, Capillary density (capillary#/mm2) in patients below or above the median value for right arterial pressure (RAP) and right ventricular diastolic pressure (RVDP).